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. 2006 Dec 15:2:41.
doi: 10.1186/1744-9081-2-41.

The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD)

Terje Sagvolden  1
Affiliations

The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD)

Terje Sagvolden. Behav Brain Funct. .

Abstract

Background: ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. While dopamine release is decreased in SHR prefrontal cortex, norepinephrine concentrations are elevated. The noradrenergic system appears to be hyperactive as a result of impaired alpha-2A adrenoceptor regulation. Thus, the present study tested behavioral effects of the centrally acting alpha-2A adrenoceptor agonist guanfacine on SHR behavior.

Methods: The present study tested behavioral effects of guanfacine at doses of 0.075, 0.15, 0.30 and 0.60 mg base/kg i.p. in both male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness.

Results: The striking impulsiveness, overactivity, and reduced sustained attention during baseline conditions in the SHR improved by treatment with guanfacine. The most pronounced improvement in SHR behavior was seen following the two highest doses (0.3 and 0.6 mg/kg) of guanfacine when SHR behaviors virtually normalized. The positive effects of the drug were most marked towards the end of the session.

Conclusion: The results indicate that guanfacine improved poor noradrenergic modulation of neuronal circuits that involve the frontal lobes in an animal model of ADHD. The present results support the beneficial effects of guanfacine on ADHD behavior reported clinically and experimentally in primate models of frontal function. It is likely that guanfacine improved prefrontal functions in the SHR. It cannot be concluded, however, that the effects of the drug are mediated solely by norepinephrine.

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Figures

Figure 1
Figure 1
Effect of the different guanfacine doses on total number of lever presses in SHR and WKY. Means ± 95% confidence intervals.
Figure 2
Figure 2
Effect of the different guanfacine doses on total number of lever presses across the five 18-min within-session segments in SHR and WKY. Means ± 95% confidence intervals.
Figure 3
Figure 3
Effect of the different guanfacine doses on impulsiveness (lg10 transformed), responding within 0.67 s following the previous lever press, in SHR and WKY. Means ± 95% confidence intervals.
Figure 4
Figure 4
Effect of the different guanfacine doses on impulsiveness (lg10 transformed) across the five 18-min within-session segments in SHR and WKY. Means ± 95% confidence intervals.
Figure 5
Figure 5
Effect of the different guanfacine doses on sustained attention, percent choice of the correct lever in SHR and WKY. Means ± 95% confidence intervals.
Figure 6
Figure 6
Effect of the different guanfacine doses on sustained attention, percent choice of the correct lever across the five 18-min within-session segments in SHR and WKY. Means ± 95% confidence intervals.
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References

    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders: DSM-IV. 4. Washington, D.C., Author; 1994. pp. 78–85.
    1. Sagvolden T, Archer T. Future perspectives on ADD research -- An irresistible challenge. In: Sagvolden T and Archer T, editor. Attention deficit disorder: Clinical and basic research. Hillsdale, N.J., Lawrence Erlbaum Associates; 1989. pp. 369–389.
    1. Johansen EB, Aase H, Meyer A, Sagvolden T. Attention-deficit/hyperactivity disorder (ADHD) behaviour explained by dysfunctioning reinforcement and extinction processes. Behav Brain Res. 2002;130:37–45. doi: 10.1016/S0166-4328(01)00434-X. - DOI - PubMed
    1. Sagvolden T, Johansen EB, Aase H, Russell VA. A dynamic developmental theory of Attention-Deficit/Hyperactivity Disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes. Behav Brain Sci. 2005;28:397–419. doi: 10.1017/S0140525X05000075. - DOI - PubMed
    1. Johansen EB, Sagvolden T, Aase H, Russell VA. The dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD): Present status and future perspectives. Behav Brain Sci. 2005;28:451–454. doi: 10.1017/S0140525X05430071. - DOI - PubMed

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